诱导多能性干细胞研究进展

人类诱导多能性干细胞（iPS细胞）的出现被誉为生命科学领域里新的里程碑,它建立了一种全新的、相对易操作而较稳定的体细胞核重编程方法,在生物学基础研究和临床应用方面具有潜在的价值;然而,iPS细胞的高癌变率和极低的重编程效率大大限制了它的应用。目前iPS细胞技术正在被不断完善,就iPS细胞的研究历程及在诱导iPS细胞上的最新研究进展进行综述。     

生成iPS细胞的快速方法

Nature报道，RudoIf Jaenisch其同事发现，通过Oct4、Sox2、Klf4和c—Myc转录因子的过度表达来对体细胞直接进行重新编程以生成诱导多能干（iPS）细胞，是一个连续的随机过程，在该过程中几乎所有供体细胞最终都将产生iPS细胞。重要的是，因为iPS细胞的生成相对来说仍然比较慢，效率比较低，所以研究人员提出了加快这一过程的两种方法：一是通过加快细胞分裂的速度；二是通过独立于细胞分裂速度的Nanog过度表达。     

维甲酸诱导小鼠iPS细胞向神经细胞分化

目的:研究小鼠诱导性多能干细胞(induced pluripotent stem cells,iP S细胞)在体外维甲酸(retinoic acid,RA)的诱导下能否分化成功能性的神经细胞。方法:首先将iPS细胞悬浮培养形成拟胚体,利用RA将其诱导分化成神经前体细胞,然后利用免疫荧光染色技术观察小鼠iPS细胞在体外分化成神经细胞以及突触发生的形态特征。结果:小鼠iPS细胞在RA的诱导下不但能够分化为成熟神经元与胶质细胞还可以观察到树突棘及突触连接的形成。结论:RA作为一种作用很强的分化诱导剂,可以有效的诱导小鼠iPS细胞分化为功能性的神经元和神经胶质细胞,这对其进行后续的神经发育的机制、药物筛选以及自体iPS细胞移植的研究具有重要意义。     

用iPS细胞进行安全治疗的方法

据2010年7月13日美国《国家科学院学报》报道，日本庆应义塾大学和京都大学研究人员调查诱导多功能干细胞（iPS细胞）发育成癌细胞的风险，发现了一种安全性很高的iPS细胞。随后他们利用这种iPS细胞进行治疗，成功恢复了脊髓受损老鼠的行动能力。iPS细胞拥有发育成各种细胞的能力．但也存在发育成癌细胞的危险。而日本研究人员日前开发的一种新方法解决了这个难题。     

转录因子调节的体细胞重编程分子和表观机制

诱导性多能干细胞(induced pluripotent stem cells,iPS)是通过转录因子诱导的体细胞重编程建立的,它与胚胎干细胞具有共同的发育多潜能性及在细胞替代治疗上潜在的应用前景。然而,转录因子调节的重编程过程是一个复杂而漫长的过程,涉及大量、未知的分子及表观事件,而且产生的iPS细胞发育潜能差异较大。对其重编程机制的揭示,将有助于获得更高效、安全的iPS细胞,为最终实现应用于人类疾病的治疗提供理论依据。本文关注了近几年转录因子调节的重编程分子机制的研究,阐述了重编程过程中转录与表观的变化。     

诱导性多潜能干细胞技术及应用研究进展

 对诱导性多潜能干细胞（iPS细胞）的研究技术进展、临床应用前景以及存在问题等方面进行了综述。     

诱导多能性干细胞技术的进展

将人类体细胞诱导成为多能性干细胞(induced pluripotent stem cells,iPS cells)的研究成果为生物医学研究提供了广泛的前景,建立了一种全新的体细胞核重编程的方法,这种方法相对容易操作,而且比较稳定、安全,点燃了再生医学应用的新希望,本文从体细胞重编程的研究历程、iPS细胞技术的诱导因子、转录因子、载体及其应用价值方面进行了综述.     

诱导多能干细胞诱导体系研究现状及进展

体细胞诱导重编程为诱导多能干细胞是近年来干细胞研究领域一项新的技术,不仅为体细胞重编程去分化机制的研究注入了新的活力,而且为疾病发生发展相关机制研究及再生医学带来了新的曙光.诱导多能干细胞（iPS细胞）诱导体系作为该技术的核心部分,在转录因子的组成和导入方式、诱导效率及诱导安全性的提高等方面都有不断的进展.就近几年iPS细胞诱导体系的现状与应用前景进行综述和展望.     

iPS细胞治肾功能不全

<正>近日,京都大学iPS细胞研究所与日本一家大型制药公司合作,用iPS细胞研制的肾脏细胞成功治愈了急性肾功能不全。研究人员扎紧试验用小鼠的血管,使其出现肾功能不全症状。然后,给小鼠移植了用的iPS细胞制成的肾脏细胞。结果发现,不用人工透析成功地治愈了急性肾功能不全。目前,正在通过其他动物试验来确认iPS细胞的安全性与有效性,估计将在2025年以后开始进行临床     

科学家开发出更安全的干细胞培养技术

美国威斯康星大学麦迪逊分校科学家最近开发出一种培养人类诱导多功能干细胞（iPS细胞）的新技术,利用这种技术培养出的iPS细胞不含病毒载体或外来基因．安全性更高。     

Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC

Previously, we found that the delivery of mouse ES (mES) cell-derived proteins to adult fibroblasts enables the full reprogramming of these cells, converting them to mouse pluripotent stem cells (protein-iPS cells) without transduction of defined factors. During reprogramming, global gene expression and epigenetic status such as DNA methylation and histone modifications convert from somatic to ES-equivalent status. mES cell extract-derived iPS cells are biologically and functionally indistinguishable from mES cells in its potential in differentiation both in vitro and in vivo. Furthermore, these cells show complete developmental potency. However, the efficiency of generating iPS by treatment with extract from mES cells is still low. In this report, we demonstrated that protein extracts of mouse iPS cells that were previously generated by mES cell extract treatment were able to reprogram somatic cells to become ES-like cells (secondary protein-iPS cells). We confirmed that fetal animals (E12.5) could be derived from these cells. Surprisingly, the efficiency of forming Oct4-positive colonies was remarkably improved by treatment of somatic cells with mouse iPS cell extract in comparison to treatment with mES cell extract. By screening the genes differentially expressed between mouse iPS and mES cells, Zscan4, which is known to enhance telomere elongation and stabilize genomic DNA, was identified as a strong candidate to promote efficiency of reprogramming. Interestingly, treatment with protein extracted from mES cells overexpressing Zscan4 enhanced formation of Oct4-positive colonies. Our results provide an efficient and safe strategy for reprogramming somatic cells by using mouse iPS cell extract. Zscan4 might be a key molecule involved in the demonstrated improvement of reprogramming efficiency.     

Residual undifferentiated cells during differentiation of induced pluripotent stem cells in vitro and in vivo

Induced pluripotent stem (iPS) cells are a potential cell source for regenerative medicine. However, the tumorigenicity of iPS cells is a big concern for clinical application. In addition to the genetic manipulation of the reprogramming process and the greater risk of tumor formation, it is unclear whether iPS cells with normal development potential are still tumorigenic. Here, we investigated 3 mouse iPS cell lines, including one line that is able to generate full-term mice via tetraploid blastocyst complementation. We found that a small number of undifferentiated iPS cells could be steadily isolated and expanded after long-term differentiation of cells in vitro or in vivo. The residual undifferentiated iPS cells could be expanded and redifferentiated, and undifferentiated pluripotent stem cells could again be isolated after further rounds of differentiation, suggesting that residual undifferentiated iPS cells could not be eliminated by extended cell differentiation. The residual undifferentiated cells could form teratomas in vivo, indicating that they are a potential tumorigenic risk during transplantation. These findings prompt us to reconsider the strategies for solving the tumorigenic problem of iPS cells, not only focusing on improving the reprogramming process.     

诱导多能干细胞建系过程中关键转录因子的作用

通过添加OCT4、SOX2等转录因子,体外诱导细胞重编程获得诱导多能干细胞是近年干细胞领域的一大突破.OCT4、SOX2和NANOG等转录因子在启动细胞重编程、维持诱导多能干细胞多能性和决定其是否走向分化方面起了关键作用.对这些转录因子作用机制的了解,有助于细胞莺编程分子机制的进一步阐明.     

Cyclin a(1) is essential for setting the pluripotent state and reducing tumorigenicity of induced pluripotent stem cells

The proper differentiation and threat of cancer rising from the application of induced pluripotent stem (iPS) cells are major bottlenecks in the field and are thought to be inherently linked to the pluripotent nature of iPS cells. To address this question, we have compared iPS cells to embryonic stem cells (ESCs), the gold standard of ground state pluripotency, in search for proteins that may improve pluripotency of iPS cells. We have found that when reprogramming somatic cells toward pluripotency, 1%-5% of proteins of 5 important cell functions are not set to the correct expression levels compared to ESCs, including mainly cell cycle proteins. We have shown that resetting cyclin A(1) protein expression of early-passage iPS cells closer to the ground state pluripotent state of mouse ESCs improves the pluripotency and reduces the threat of cancer of iPS cells. This work is a proof of principle that reveals that setting expression of certain proteins correctly during reprogramming is essential for achieving ESC-state pluripotency. This finding would be of immediate help to those researchers in different fields of iPS cell work that specializes in cell cycle, apoptosis, cell adhesion, cell signaling, and cytoskeleton.